Osteoarthritis (OA) is a common disabling disorder for which no good medical remedy currently exists. As a result, many patients take Glucosamine, a nutritional supplement, for the treatment of their OA symptoms, because of its high level of safety compared to traditional anti-inflammatory medications. However, oral glucosamine is promptly metabolized by the liver during first-pass metabolism. Injectable polyglucosamine (PGA) is a highly viscous sustained-release form of glucosamine which may prove a more efficient modality for delivering glucosamine to the joint. The overall goal of this proposed Phase I SBIR is to determine if intraarticular injections of PGA protect against the early stages of joint damage in a rabbit model of OA. The proposed specific aims include: (1) Create a surgical instability of the knee in 14 2 Kg NZW rabbits using a modification of the Hulth technique. (2) Administer the PGA-treated and control groups (n=7 each) 5 weekly injections of PGA or saline respectively into the unstable knee, and maintain the animals for an additional 7 weeks. (3) Examine the extent of lesions in a blind fashion using morphological, histological and biochemical evaluations.